Comparisons between glucose analogue 2-deoxy-2-(18F)fluoro-D-glucose and 18F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

AIM: To compare 2-deoxy-2-(¹⁸F)fluoro-D-glucose(¹⁸F-FDG) and ¹⁸F-sodium (¹⁸F-NaF) positron emission tomography/computed tomography (PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases.METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent ¹⁸F-FDG and ¹⁸F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity (Se), specificity (Sp), overall accuracy, positive and negative predictive values, error rate, and Youden’s index. McNemar’s χ² test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the co-registered CT (sclerotic, lytic, mixed, no-lesions) and the divergent site of disease (skull, spine, ribs, extremities, pelvis). The impact of adding ¹⁸F-NaF PET/CT to the work-up of patients was also measured in terms of change in their management due to ¹⁸F-NaF PET/CT findings.RESULTS: The two imaging methods of ¹⁸F-FDG and ¹⁸F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively (McNemar’s χ² = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis (McNemar’s χ² = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, ¹⁸F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis (P < 0.002) and vertebral localizations (P < 0.002); ¹⁸F-NaF PET/CT was more accurate in detecting sclerotic (P < 0.005) and rib lesions (P < 0.04). ¹⁸F-NaF PET/CT led to a change of management in 3 of the 45 patients (6.6%) by revealing findings that were not detected at ¹⁸F-FDG PET/CT.CONCLUSION: ¹⁸F-FDG PET/CT is a reliable imaging tool in the detection of bone metastasis in most cases, with a diagnostic accuracy that is slightly, but significantly, superior to that of ¹⁸F-NaF PET/CT in the general population of breast cancer patients. However, the extremely high sensitivity of ¹⁸F-fluoride PET/CT can exploit its diagnostic potential in specific clinical settings (i.e., small CT-evident sclerotic lesions, high clinical suspicious of relapse, and negative ¹⁸F-FDG PET and conventional imaging).     

In vitro anti-inflammatory and immunomodulatory properties of umbelliprenin and methyl galbanate

Ferula species (Apiaceae) are considered important medicinal plants. The present in vitro study sought to investigate the immunomodulatory and anti-inflammatory properties of terpenoid coumarins isolated from Ferula szowitsiana on immune cells isolated from naïve mice and to elucidate possible underlying mechanisms of action. With splenocytes, effects of the agents on PHA-induced proliferation and interleukin (IL)-4 and interferon (IFN)-γ release were assessed. With peritoneal macrophages, anti-inflammatory potentials were evaluated in lipopolysaccharide (LPS)/IFNγ-stimulated cells via measures of changes in nitric oxide (NO) and PGE₂ secretion. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was also determined via Western blot analysis. The results indicated that umbelliprenin (UMB) and methyl galbanate (MG) reduced remarkably PHA-induced splenocyte proliferation and both preferentially induced T_H2 IL-4 and suppressed T_H1 IFNγ secretion. Each also significantly suppressed LPS-induced production of NO and PGE₂ apparently and also led to reductions in inducible iNOS and COX-expression. To the authors’ knowledge, the present study is the first to report on anti-inflammatory and immunomodulatory effects of UMB and MG in vitro. The present results suggest that each could potentially be exploited as a natural immunosuppressant against inflammatory and autoimmune diseases once substantial further toxicological analyses have been done to confirm overall safety in vivo.     

Polymorphism in Leptin and Leptin Receptor Genes May Modify Leptin Levels and Represent Risk Factors for Multiple Sclerosis

Background: Leptin, the product of the ob gene, can modulate the immune responses and also seems to regulate Th1/Th2 balance by promoting a shift from the Th2 to the Th1 inflammatory cytokine pathway. Therefore, in this study, we aimed to investigate the association between polymorphisms of leptin gene (LEP) and leptin receptor gene (LEPR) and susceptibility to multiple sclerosis (MS). In addition, we investigated the influence of these two common polymorphisms on plasma levels of leptin.

Methods: This case–control study was conducted on 232 MS patients and 204 control subjects. Serum level measurement of leptin was performed using enzyme-linked immunosorbent assay (ELISA). G-2548-A LEP polymorphism and 223A/G polymorphism of the LEPR were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: There was a significant difference in allele/genotype frequencies of LEP gene among MS patients and control subjects (p<0.01). The genotype frequencies of LEPR polymorphism were also significantly different between control subjects and MS patients (p=0.02). The mean serum level of leptin was significantly higher in MS patients as compared with the controls (p<0.01).

Conclusion: Our study implicates a significant role of LEP and LEPR polymorphisms and also leptin levels in the risk of MS and its severity. Furthermore, our findings suggest LEP and LEPR polymorphisms as important predictors for increased serum leptin in Iranian MS patients. Although this study provides new clinically relevant information regarding genetic determinants modulating risk of MS, further investigations are necessary to understand better the mechanistic implications of these observations in the development of MS.     

Increasing proliferation of murine adipose tissue-derived mesenchymal stem cells by TNF-α plus IFN-γ

The objective of the current study was to assess the effects of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) along with their simultaneous application on proliferation and pluripotency genes of murine adipose tissue-derived mesenchymal stem cells (AT-MSCs). The proliferation, doubling time (DT), colony-forming unit–fibroblast (CFU-F), pluripotency genes expression, and proliferation-related immunomodulatory markers of MSCs were analyzed upon activation with TNF-α (10?ng/ml), IFN-γ (10?ng/ml) and both TNF-α and IFN-γ (5?ng/ml?+?5?ng/ml). Pluripotency genes including Oct-4, Sox-2, and Nanog as well as proliferation-associated immunomodulatory cytokines such as insulin-like growth factor 1 (IGF-1) and transforming growth factor-β (TGF-β) expression were evaluated using real-time PCR. Surface expression of Qa2 (HLA-G) was analyzed by flow cytometry. Pretreatment of MSCs with TNF-α plus IFN-γ led to significantly increased proliferation, DT and CFU-F as well as expression of pluripotency genes in AT-MSCs (p < 0.01). MSCs expressed more IGF-1, TGF-β, and Qa2 upon activation with TNF-α plus IFN-γ and IFN-γ. MSCs expressed significantly decreased amounts of TGF-β and Qa2 in presence of TNF-α. TNF-α combined with IFN-γ may be improved the proliferation of AT-MSCs. Conversely, expanded MSCs pointed out low levels of the immunomodulatory marker, s especially Qa2 in the presence of TNF-α. In conclusion, we showed that TNF-α together with IFN-γ increased the proliferation of MSCs and slightly enhanced the expression of pluripotency genes.     

Knowledge, attitude and practice towards droplet and airborne isolation precautions among dental health care professionals in Shiraz, Iran

OBJECTIVE: To determine the level of knowledge, attitude and practice among Iranian dental health care professionals towards droplet and airborne isolation precautions, in Shiraz, Iran. METHODS: A survey was developed and distributed to 152 Iranian dental professionals (faculty and students) from Shiraz University School of Medical Sciences, School of Dentistry, Shiraz, Iran. The self-administered questionnaire was composed of three parts (knowledge, attitude, and practice). After validation of the survey using the Kuder Richardson reliability test and Cronbach's alpha internal consistency coefficient, data was collected and analyzed using Analysis of Variance and the Duncan test to detect the differences among groups. The Spearman coefficient was used to determine the correlation between knowledge, attitude, and practice. RESULTS: The survey was completed by 152 (51.5%) of 295 potential respondents. Mean scores of knowledge, attitude, and practice towards droplets and airborne isolation precautions were poor (98 +/- 3.45, 10.51 +/- 6.26, 2.68 +/- 3.16 from the maximum scores of 11, 55, and 11, respectively). In addition, a positive linear correlation was found between two items of the survey including knowledge-attitude (rho = 0.438, p < 0.001), knowledge and practice (rho = 0.380, p < 0.001). CONCLUSION: Iranian dental professionals seemed to have low levels of knowledge, attitude and practice towards infection control.     

The need for venovenous bypass in liver transplantation

Since introduction of the conventional liver transplantation (CLTx) by Starzl, which was based on the resection of recipient inferior vena cava (IVC) along the liver, the procedure has undergone several refinements. Successful use of venovenous bypass (VVB) was first introduced by Shaw et al., although in recent decades there has been controversy regarding the routine use of VVB during CLTx. With development of piggyback liver transplantation (PLTx), the use of caval clamping and VVB is avoided, leading to fewer complications related to VVB. However, some authors still advocate VVB in PLTx. The great diversity among centers in their use of VVB during CLTx, or even along the PLTx technique, has led to confusion regarding the indication setting for VVB. For this reason, we present an overview of the use of VVB in CLTx, the target of patients for whom VVB could be beneficial, and the needs assessment of VVB for patients undergoing PLTx. Recent studies have shown that with the advancement of surgical skills, refinement of surgical techniques, and improvements in anesthesiology, there are only limited indications for doing CLTx with VVB routinely. PLTx with preservation of IVC can be performed in almost all primary transplants and in the majority of re-transplantations without the need for VVB. Nevertheless, in a few selective cases with severe intra-operative hemodynamic instability, or with a failed test of transient IVC occlusion, the application of VVB is still justifiable. These indications should be judged intra-operatively and the decision is based on each center's preference.